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The mol­ecule of the title compound, C16H21NO4, is chiral and has three asymmetric centres. The absolute configuration was not determined via diffraction measurements on the crystal, but was established from the known absolute configuration of the starting material. In the crystal structure, the mol­ecules assemble through inter­molecular hydrogen bonds into a macrostructure with helical channels.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270106004884/av1281sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270106004884/av1281Isup2.hkl
Contains datablock I

CCDC reference: 605689

Comment top

Chiral auxiliary-based aldol reactions have been the focus of much interest as the strategy of choice for accessing single isomers of β-hydroxy acid derivatives as chiral building blocks for bioactive compounds (Evans et al., 1981; Ager et al., 1996, 1997; Arya et al., 2000; Evans, Downey et al., 2002; Evans, Tedrow et al., 2002). We recently reported that the use of a new N-acyl phenyliminooxazolidine auxiliary resulted in high diastereoselectivity in alkylation reactions (Lee et al., 2002). During our ongoing studies of chiral auxiliary-based asymmetric reactions, the unexpected title compound, (I), was formed in an aldol reaction and its structure is reported here.

Compound (I) has three chiral C atoms and is one of eight possible stereoisomers. Crystallographically, the absolute configuration has not been established by anomalous dispersion effects, but the R and S configurations of the chiral centres could be assigned by reference to an unchanging asymmetric centre in the reaction procedure. Atoms C7, C8 and C13 have S, R and S configurations, respectively (Fig. 1).

In the crystal structure, molecules of (I) are assembled by two intermolecular hydrogen-bonding interactions, viz. O1—H1···O2i and C12—H12a···O4ii, with O1···O2i = 2.871 (3) Å and C12···O4ii = 3.369 (4) Å [symmetry codes: (i) 1 − x, 1/2 + y, −z; (ii) 1 − x, −1/2 + y, 1 − z]. Atom O1 of the alcohol group and atom C12 in the oxazolidinone ring act as hydrogen-bond donors, and atoms O2 and O4 of the ketone groups act as acceptors (Table 2). The molecules are extended via the hydrogen bonds into a macrostructure, with a left-handed helical chain (O1—H1···O2i; Fig. 2) and a right-handed helical chain (C12—H12A···O4ii; Fig. 3) along the b axis. The cavity of the channel in Fig. 2 has a minimum diameter of 2.816 Å. The molecules stack in layers along the b axis, and the distance between the layers is 6.175 Å. The side view of the hydrogen-bonded left-handed helical chain structure is shown in Fig. 4. The helices are packed in a hexagonal-based array.

Examination of the structure with PLATON (Spek, 2003) reveals a short ring–ring interaction (<6 Å) for oxazolidinone rings. The centroid–centroid distance between Cg1 (the centroid of the five-membered ring O3–C12) and Cg1ii [symmetry code: (ii) 1 − x, −1/2 + y, 1 − z] is 4.222 Å, and the dihedral angle between the ring planes is 35.9°. For phenyl rings, the shortest distance between Cg2 (the centroid of the phenyl ring C1–C6) and Cg2iii [symmetry code: (iii) −x, −1/2 + y, −z] is 5.175 Å, and the dihedral angle is 42.2°.

Experimental top

The title compound was synthesized following an analogous procedure to that described by Evans, Downey et al. (2002) for related compounds. To a round-bottomed flask in a glove box was added MgBr2·OEt2 (36 mg, 0.5 equivalents). The flask was fitted with a septum cap and removed to an ambient atmosphere, where it was charged with N-acylated phenyliminooxazolidine (0.28 mmol, 72 mg, 1 equivalent), EtOAc (3 ml), benzaldehyde (0.30 mmol, 31 µl, 1.1 equivalents), Et3N (0.55 mmol, 77 µl, 2 equivalents) and trimethylsilyl chloride (0.41 mmol, 53 µl, 1.5 equivalents). The reaction mixture was stirred for 26 h and then filtered directly through a plug of silica gel (5.5 cm × 4.0 cm) and eluted with Et2O. The eluent was concentrated and dissolved in tetrahydrofuran (50 ml) and treated with 1.0 N HCl (10 ml). After stirring for 1 h, the mixture was diluted with Et2O (100 ml) and water (100 ml). The organic layer was extracted with saturated NaHCO3 (50 ml), dried, filtered and concentrated. Flash chromatography (EtOAc–hexane = 2:8) afforded pure compound (I) in 58% yield. Single crystals suitable for an X-ray diffraction study were obtained by slow evaporation of a toluene solution over a period of one week. Spectroscopic analysis: 1H NMR (CDCl3, δ, p.p.m.): 7.42–7.29 (m, 5H), 4.75 (bt, 1H, J = 6.3 Hz), 4.46–4.17 (m, 4H), 3.17 (bd, 1H, J = 6.6 Hz), 2.30–2.23 (m, 1H), 1.10 (d, 1H, J = 6.9 Hz), 0.87 (d, 1H, J = 7.1 Hz), 0.70 (d, 1H, J = 6.9 Hz); 13C NMR (CDCl3, δ, p.p.m): 176.7, 154.2, 142.2, 128.5, 128.0, 126.5, 77.4, 63.2, 58.8, 43.9, 28.3, 17.9, 14.8, 14.3; MS (EI) m/z 291 (M+).

Refinement top

In the absence of significant anomalous scattering, Friedel opposites were merged. All H atoms were positioned geometrically and allowed to ride on their respective carrier atoms, with O1—H = 0.83 Å and Uiso(H) = 1.5Ueq(O1), and C—H = 0.94–0.99 Å and Uiso(H) = 1.2Ueq(C) or 1.5Ueq(C).

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SMART; data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures top
[Figure 1] Fig. 1. The structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are represented by circles of arbitrary size.
[Figure 2] Fig. 2. A view of the O1—H1···O2i hydrogen-bond interactions (dashed lines) in the crystal structure of (I). [Symmetry code: (i) 1 − x, 1/2 + y, −z.]
[Figure 3] Fig. 3. A view of the C12—H12A···O4ii hydrogen-bond interactions (dashed lines) in the crystal structure of (I). [Symmetry code: (ii) 1 − x, −1/2 + y, 1 − z.]
[Figure 4] Fig. 4. A side view of the hydrogen-bonded left-handed helical chain structure along the b axis. Dashed lines indicate hydrogen bonds. [Symmetry code: (i) 1 − x, 1/2 + y, −z.]
(4S)-3-[(2R,3S)-3-Hydroxy-2-methyl-3-phenylpropionyl]-4- isopropyloxazolidin-2-one top
Crystal data top
C16H21NO4F(000) = 312
Mr = 291.34Dx = 1.220 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 634 reflections
a = 11.6191 (10) Åθ = 1.8–28.2°
b = 6.1749 (5) ŵ = 0.09 mm1
c = 12.0431 (10) ÅT = 243 K
β = 113.394 (2)°Block, colourless
V = 793.02 (11) Å30.1 × 0.1 × 0.1 mm
Z = 2
Data collection top
Bruker SMART 1000 area-detector CCD
diffractometer
908 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.041
Graphite monochromatorθmax = 28.2°, θmin = 1.8°
ϕ and ω scansh = 1510
5052 measured reflectionsk = 77
1976 independent reflectionsl = 1215
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.040Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.061H-atom parameters constrained
S = 0.82 w = 1/[σ2(Fo2) + (0.0121P)2]
where P = (Fo2 + 2Fc2)/3
1976 reflections(Δ/σ)max < 0.001
194 parametersΔρmax = 0.10 e Å3
1 restraintΔρmin = 0.11 e Å3
Crystal data top
C16H21NO4V = 793.02 (11) Å3
Mr = 291.34Z = 2
Monoclinic, P21Mo Kα radiation
a = 11.6191 (10) ŵ = 0.09 mm1
b = 6.1749 (5) ÅT = 243 K
c = 12.0431 (10) Å0.1 × 0.1 × 0.1 mm
β = 113.394 (2)°
Data collection top
Bruker SMART 1000 area-detector CCD
diffractometer
908 reflections with I > 2σ(I)
5052 measured reflectionsRint = 0.041
1976 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0401 restraint
wR(F2) = 0.061H-atom parameters constrained
S = 0.82Δρmax = 0.10 e Å3
1976 reflectionsΔρmin = 0.11 e Å3
194 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.3867 (2)0.5784 (3)0.01675 (19)0.0666 (7)
H10.37710.61810.05220.100*
O20.59887 (19)0.2834 (4)0.19135 (19)0.0580 (7)
O30.5394 (2)0.5608 (4)0.5043 (2)0.0650 (7)
O40.3574 (2)0.5237 (4)0.3468 (2)0.0702 (8)
N10.5480 (2)0.4363 (4)0.3336 (2)0.0457 (7)
C10.2101 (3)0.3282 (6)0.0618 (3)0.0517 (9)
C20.1648 (3)0.1345 (6)0.1206 (3)0.0649 (11)
H20.22180.02470.11800.078*
C30.0374 (4)0.0980 (7)0.1833 (3)0.0880 (15)
H30.00820.03520.22210.106*
C40.0449 (4)0.2597 (10)0.1877 (4)0.0995 (18)
H40.13150.23810.23070.119*
C50.0016 (4)0.4551 (9)0.1293 (4)0.0979 (15)
H50.05880.56460.13170.118*
C60.1252 (3)0.4886 (6)0.0680 (3)0.0721 (11)
H60.15420.62230.02990.086*
C70.3484 (3)0.3568 (5)0.0130 (3)0.0496 (9)
H70.39760.26420.01920.059*
C80.3773 (3)0.2981 (5)0.1433 (3)0.0483 (9)
H80.32470.38770.17290.058*
C90.3540 (3)0.0572 (6)0.1603 (3)0.0721 (11)
H9A0.40570.03160.13190.108*
H9B0.26630.02310.11440.108*
H9C0.37550.02830.24540.108*
C100.5143 (3)0.3415 (5)0.2209 (3)0.0501 (9)
C110.4686 (4)0.5044 (5)0.3881 (3)0.0537 (10)
C120.6692 (3)0.5064 (6)0.5352 (3)0.0700 (11)
H12A0.69330.38060.58920.084*
H12B0.72350.62840.57600.084*
C130.6814 (3)0.4554 (5)0.4176 (3)0.0540 (10)
H130.72260.31270.42460.065*
C140.7530 (3)0.6226 (6)0.3781 (3)0.0656 (11)
H140.75020.57650.29840.079*
C150.8895 (3)0.6271 (6)0.4650 (4)0.1254 (19)
H15A0.93880.69740.42660.188*
H15B0.91930.48010.48690.188*
H15C0.89780.70670.53730.188*
C160.6968 (4)0.8484 (6)0.3626 (4)0.1024 (16)
H16A0.61200.84550.30110.154*
H16B0.74730.94740.33810.154*
H16C0.69540.89660.43870.154*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0718 (16)0.0637 (17)0.0633 (16)0.0116 (15)0.0256 (14)0.0064 (14)
O20.0506 (15)0.0655 (17)0.0608 (16)0.0009 (14)0.0250 (12)0.0111 (13)
O30.0760 (18)0.0653 (16)0.0523 (15)0.0091 (15)0.0240 (13)0.0128 (14)
O40.0597 (16)0.087 (2)0.0664 (16)0.0104 (17)0.0270 (13)0.0065 (15)
N10.0475 (17)0.0444 (18)0.0429 (17)0.0014 (14)0.0158 (14)0.0008 (14)
C10.045 (2)0.066 (3)0.044 (2)0.003 (2)0.0167 (17)0.005 (2)
C20.057 (3)0.081 (3)0.054 (2)0.003 (2)0.0191 (19)0.007 (2)
C30.071 (3)0.099 (4)0.072 (3)0.023 (3)0.005 (2)0.006 (3)
C40.053 (3)0.131 (5)0.087 (4)0.023 (3)0.001 (3)0.034 (3)
C50.062 (3)0.111 (4)0.119 (4)0.023 (3)0.035 (3)0.037 (3)
C60.056 (3)0.067 (3)0.091 (3)0.002 (2)0.027 (2)0.007 (2)
C70.050 (2)0.046 (2)0.055 (2)0.003 (2)0.0234 (18)0.0035 (19)
C80.043 (2)0.058 (2)0.046 (2)0.002 (2)0.0189 (16)0.0029 (19)
C90.070 (2)0.075 (3)0.061 (2)0.022 (2)0.0162 (18)0.014 (2)
C100.054 (2)0.046 (2)0.050 (2)0.005 (2)0.0201 (19)0.0001 (19)
C110.067 (3)0.042 (2)0.052 (2)0.002 (2)0.024 (2)0.0035 (19)
C120.067 (3)0.078 (3)0.054 (2)0.016 (2)0.011 (2)0.000 (2)
C130.051 (2)0.041 (2)0.057 (2)0.0006 (18)0.0083 (18)0.0027 (19)
C140.060 (2)0.068 (3)0.068 (3)0.018 (2)0.025 (2)0.014 (2)
C150.051 (3)0.108 (4)0.188 (5)0.020 (3)0.016 (3)0.016 (4)
C160.110 (4)0.059 (3)0.141 (4)0.011 (3)0.053 (3)0.029 (3)
Geometric parameters (Å, º) top
O1—C71.434 (3)C7—H70.9900
O1—H10.8300C8—C101.517 (4)
O2—C101.224 (3)C8—C91.540 (4)
O3—C111.357 (3)C8—H80.9900
O3—C121.443 (3)C9—H9A0.9700
O4—C111.192 (3)C9—H9B0.9700
N1—C101.384 (4)C9—H9C0.9700
N1—C111.392 (4)C12—C131.512 (4)
N1—C131.482 (4)C12—H12A0.9800
C1—C61.379 (4)C12—H12B0.9800
C1—C21.383 (4)C13—C141.516 (4)
C1—C71.508 (4)C13—H130.9900
C2—C31.387 (4)C14—C151.514 (4)
C2—H20.9400C14—C161.519 (4)
C3—C41.369 (5)C14—H140.9900
C3—H30.9400C15—H15A0.9700
C4—C51.387 (6)C15—H15B0.9700
C4—H40.9400C15—H15C0.9700
C5—C61.376 (5)C16—H16A0.9700
C5—H50.9400C16—H16B0.9700
C6—H60.9400C16—H16C0.9700
C7—C81.512 (4)
C7—O1—H1109.5H9A—C9—H9C109.5
C11—O3—C12110.4 (3)H9B—C9—H9C109.5
C10—N1—C11127.4 (3)O2—C10—N1117.5 (3)
C10—N1—C13121.0 (3)O2—C10—C8122.4 (3)
C11—N1—C13111.3 (3)N1—C10—C8119.9 (3)
C6—C1—C2118.3 (3)O4—C11—O3121.1 (3)
C6—C1—C7121.2 (3)O4—C11—N1130.2 (3)
C2—C1—C7120.4 (3)O3—C11—N1108.7 (3)
C1—C2—C3121.8 (4)O3—C12—C13106.5 (2)
C1—C2—H2119.1O3—C12—H12A110.4
C3—C2—H2119.1C13—C12—H12A110.4
C4—C3—C2118.7 (4)O3—C12—H12B110.4
C4—C3—H3120.7C13—C12—H12B110.4
C2—C3—H3120.7H12A—C12—H12B108.6
C3—C4—C5120.5 (4)N1—C13—C12101.2 (3)
C3—C4—H4119.7N1—C13—C14113.4 (3)
C5—C4—H4119.7C12—C13—C14114.8 (3)
C6—C5—C4119.9 (5)N1—C13—H13109.1
C6—C5—H5120.1C12—C13—H13109.1
C4—C5—H5120.1C14—C13—H13109.1
C5—C6—C1120.8 (4)C15—C14—C13110.5 (3)
C5—C6—H6119.6C15—C14—C16110.4 (3)
C1—C6—H6119.6C13—C14—C16113.6 (3)
O1—C7—C1112.0 (3)C15—C14—H14107.3
O1—C7—C8104.9 (3)C13—C14—H14107.3
C1—C7—C8109.7 (3)C16—C14—H14107.3
O1—C7—H7110.1C14—C15—H15A109.5
C1—C7—H7110.1C14—C15—H15B109.5
C8—C7—H7110.1H15A—C15—H15B109.5
C7—C8—C10110.1 (3)C14—C15—H15C109.5
C7—C8—C9113.1 (3)H15A—C15—H15C109.5
C10—C8—C9106.6 (3)H15B—C15—H15C109.5
C7—C8—H8109.0C14—C16—H16A109.5
C10—C8—H8109.0C14—C16—H16B109.5
C9—C8—H8109.0H16A—C16—H16B109.5
C8—C9—H9A109.5C14—C16—H16C109.5
C8—C9—H9B109.5H16A—C16—H16C109.5
H9A—C9—H9B109.5H16B—C16—H16C109.5
C8—C9—H9C109.5
C6—C1—C2—C30.9 (5)C9—C8—C10—O276.2 (4)
C7—C1—C2—C3175.6 (3)C7—C8—C10—N1137.9 (3)
C1—C2—C3—C40.7 (6)C9—C8—C10—N199.1 (3)
C2—C3—C4—C50.7 (7)C12—O3—C11—O4175.5 (3)
C3—C4—C5—C61.0 (7)C12—O3—C11—N16.9 (4)
C4—C5—C6—C11.3 (6)C10—N1—C11—O410.9 (6)
C2—C1—C6—C51.2 (5)C13—N1—C11—O4175.2 (4)
C7—C1—C6—C5175.3 (3)C10—N1—C11—O3171.7 (3)
C6—C1—C7—O132.2 (4)C13—N1—C11—O32.1 (4)
C2—C1—C7—O1151.4 (3)C11—O3—C12—C1313.0 (4)
C6—C1—C7—C883.8 (4)C10—N1—C13—C12164.8 (3)
C2—C1—C7—C892.6 (4)C11—N1—C13—C129.5 (4)
O1—C7—C8—C1055.6 (3)C10—N1—C13—C1471.8 (4)
C1—C7—C8—C10176.0 (3)C11—N1—C13—C14113.9 (3)
O1—C7—C8—C9174.6 (3)O3—C12—C13—N113.0 (3)
C1—C7—C8—C965.0 (4)O3—C12—C13—C14109.4 (3)
C11—N1—C10—O2176.6 (3)N1—C13—C14—C15177.7 (3)
C13—N1—C10—O23.3 (4)C12—C13—C14—C1566.7 (4)
C11—N1—C10—C81.1 (5)N1—C13—C14—C1657.5 (4)
C13—N1—C10—C8172.3 (3)C12—C13—C14—C1658.1 (4)
C7—C8—C10—O246.8 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O2i0.832.072.871 (3)161
C12—H12A···O4ii0.982.483.369 (4)150
Symmetry codes: (i) x+1, y+1/2, z; (ii) x+1, y1/2, z+1.

Experimental details

Crystal data
Chemical formulaC16H21NO4
Mr291.34
Crystal system, space groupMonoclinic, P21
Temperature (K)243
a, b, c (Å)11.6191 (10), 6.1749 (5), 12.0431 (10)
β (°) 113.394 (2)
V3)793.02 (11)
Z2
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.1 × 0.1 × 0.1
Data collection
DiffractometerBruker SMART 1000 area-detector CCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5052, 1976, 908
Rint0.041
(sin θ/λ)max1)0.666
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.061, 0.82
No. of reflections1976
No. of parameters194
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.10, 0.11

Computer programs: SMART (Bruker, 2000), SMART, SAINT (Bruker, 2000), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 (Farrugia, 1997), SHELXL97.

Selected geometric parameters (Å, º) top
O1—C71.434 (3)N1—C111.392 (4)
O2—C101.224 (3)N1—C131.482 (4)
O3—C111.357 (3)C1—C61.379 (4)
O3—C121.443 (3)C1—C21.383 (4)
O4—C111.192 (3)C1—C71.508 (4)
N1—C101.384 (4)C12—C131.512 (4)
C11—O3—C12110.4 (3)N1—C10—C8119.9 (3)
C11—N1—C13111.3 (3)O4—C11—O3121.1 (3)
O1—C7—C1112.0 (3)O4—C11—N1130.2 (3)
O1—C7—C8104.9 (3)O3—C11—N1108.7 (3)
C1—C7—C8109.7 (3)O3—C12—C13106.5 (2)
O2—C10—N1117.5 (3)N1—C13—C12101.2 (3)
O2—C10—C8122.4 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O2i0.832.072.871 (3)161
C12—H12A···O4ii0.982.483.369 (4)150
Symmetry codes: (i) x+1, y+1/2, z; (ii) x+1, y1/2, z+1.
 

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